Thioredoxin reductase 1, cytoplasmic (TrxR1)

Thioredoxin reductase 1, cytoplasmic (TrxR1), encoded by the TXNRD1 gene, is a cytosolic member of the pyridine nucleotide oxidoreductase family and functions primarily as an essential selenoenzyme involved in cellular redox regulation. It reduces oxidized thioredoxin (Trx) to its active, dithiol-containing form via a reaction that is dependent on NADPH and the unique selenocysteine residue at its active site[1][3][4][5][6]. This activity plays a central role in protection against oxidative stress, cell proliferation, DNA synthesis, and apoptosis. TrxR1 acts as a homodimeric flavoprotein, requiring FAD as a cofactor, and is critical for protecting cells from reactive oxygen species. The enzyme is implicated in cancer, cardiovascular, neurodegenerative, and inflammatory diseases, and is a validated drug target, most notably by the gold compound auranofin[1][3][6]. Targeting TrxR1 is associated with efficacy in some malignancies but may also present safety concerns due to its essential physiological roles.

Other names

TXNRD1TRTrxRTrxR1thioredoxin reductase 1cytosolic thioredoxin reductase

Inhibition of enzyme active site (e.g., by selenocysteine targeting), Disruption of redox homeostasis, Enhancement of oxidative stress leading to cell death (apoptosis)